Kainate Microinjection into the Dorsal Raphe Nucleus Induces 5-HT Release in the Amygdala and Periaqueductal Gray

Earlier results obtained in one of our laboratories showed that microinjection into the dorsal raphe nucleus (DRN) of the excitatory amino acid kainic acid, the benzodiazepine (BZD) inverse agonist FG 7142, and the 5-HT 1A receptor agonist 8-OH-DPAT changed the behavior of rats in the elevated T-maze, an animal model of anxiety. The present study investigates biochemical correlates of these results in awake rats by measuring 5-HT release with in vivo microdialysis in two brain structures innervated by the DRN—the amygdala (Am) and the dorsal periaqueductal gray matter (DPAG)—that have been implicated in anxiety. Microinjection of kainic acid (60 pmol) into the DRN significantly increased 5-HT release in both the Am and the DPAG. In the DPAG, the increase was 14-fold higher with respect to the baseline and occurred only at the first sample, which was collected 30 min after the injection. In the Am, the increase was less pronounced (nearly fourfold) but persistent, lasting until the fourth sample, which was collected 120 min from the injection. FG 7142 (40 pmol) and 8-OH-DPAT (8 nmol) were ineffective. Because only intra-DRN kainate both increased inhibitory avoidance and decreased one-way escape in the elevated T-maze, the present behavioral results support the suggestion that 5-HT facilitates conditioned fear in the Am and inhibits unconditioned fear in the DPAG.